System and apparatus for providing diagnosis and personalized abnormalities alerts and for providing adaptive responses in clinical trials

ABSTRACT

A personalized real-time automated cardiovascular monitoring system monitors abnormalities in a patient&#39;s cardiovascular activity data through the use of individually adjusted electrocardiogram Holter apparatus (Holter/ECG device) that provides an automatic medical diagnosis of cardiac abnormalities and generates abnormality alert signals representative of certain abnormalities in patient&#39;s cardiac activities. The signals are transmitted using a wireless network to a medical dispatcher center. A response is generated according to the abnormality detected. Individual parameters indicative of patient&#39;s cardio activities are personalized to allow for adjustments of chronic patients. A base Holter/ECG unit, includes the wireless/electric electrodes and their respective wireless/electric connections, and a Holter/ECG recording unit affixed to the base unit. Automatic real-time medical response may be provided based on automatic cardiac abnormality alert detection from the Holter/ECG data.

FIELD OF THE INVENTION

The present invention relates to cardiac monitoring system and, moreparticularly, to a Holter/ECG-type system and apparatus for real-timeautomated diagnostics of the cardiological activity of the patient. Thepresent invention also relates to a system for providing real-timemedical response in clinical trials.

BACKGROUND OF THE INVENTION

In general, there are two types of cardiovascular abnormalities tests: aone-time recording during a few seconds and a long-term monitoring whichcan be performed during regular daily activities or as a round-the-clockmonitoring in patients with serious medical disturbances. An example ofa one-time recording is an electrocardiogram (ECG) test. However ECGtest is not sufficient comprehensive because it tests only a briefperiod of time, and therefore can detect only a part of cardiovascularabnormalities.

A prime example of long-term monitoring system is a 24-hourcardiovascular monitoring Holter system which is widely used in theprior art for diagnosing cardiac abnormalities. Currently used Holterrecording devices use an analogue or digital recording technique. Datarecorded by such a holter was initially analyzed by a medicalprofessional, which amounts to many hours of expensive manual labor. Onesuch basic Holter ECG system disclosed by Elliott in U.S. Pat. No.5,398,183, another one by Thornton in U.S. Pat. No. 5,036,856.

As a next development of holter technology, computerized data analysiswas introduced. Usually, in current digital Holter systems, processingof the data consists of computerized data scanning to receive thepreliminary diagnosis with subsequent manual verification by a medicalprofessional.

Such Holter system had been developed by several companies worldwide:

-   -   Burdick Vision holters by CardiacScience Inc, a US company;    -   FM Series holters by a Japanese company Fukuda;    -   DL Series holters by Braemar Inc, another US company;    -   H-Scribe holter by Mortara, another US company;    -   DR 180 holter by NEMon;    -   Reveala by Nasan Medical, an Indian company; to name a few.

Holters mentioned above provide mainly data recording.

Lately, there have been further developments in the holters industry. Anumber of modern holters are now equipped with data analysis software.An example of such a holter is a Trillium 3000 by Forest Medical. Inthis holter all cardiological data is recorded over the 24 hours period,and at the end of the 24 hours period a report is generated using dataanalysis tool. This report is further printed and the printed report ispresented to the physician for his review. Another example of a holterwith analyzing capabilities is the one presented by the Epicardia HolterSystems, where after finishing data recording, the technician can scanthe recorder data and generate a report on events detected.

An example of Holter system with analysis capabilities was presented byGallant in U.S. Pat. No. 5,433,209 named “Recorder unit for ambulatoryECG monitoring system”.

As a further development of holter systems, there are products thatprovide transfer of cardiological data recorded through the Internet orthrough the wireless device to the clinic. I.e., data is recorded for,say, 24 hours and then, instead of visiting the clinic, the patient hasto connect to the Internet at his home computer and send the data to themedical center through the Internet. Alternatively, in other productsthe patient has to send the data from his holter to the medical centerthrough wireless device. In both cases above, the medical diagnosis and,consequently, alert on cardiovascular abnormality is in the clinic andnot in real-time. An example of such a holter is a Vision Premierdeveloped by Burdick company, which includes connectivity between theholter and various information systems, including the suite ofHeartCentrix web data management solutions. An example of holter datatransmittance through the wireless system is presented by HealthPALdevice from MedApps company that automatically collects data fromcompatible, off-the-shelf, medical monitors using a smart cable orwirelessly via Bluetooth. The data is then transmitted using embeddedM2M (GSM and CDMA) cellular chip technology to be received by HealthCOM,MedApps' full-featured, web-based portal for health care providers.

U.S. Pat. No. 6,701,184 titled “Virtual Holter” by Henkin describes suchholter that provides “ECG Holter data scanning, processing, andanalyzing system by way of obtaining a Holter recording in aconventional manner, then downloading that analog or digital data to aPC, then going online through the PC by way of an ISP, such as DSL,capable of large data transfer, through a USB to tie into a URL webaddress for a Central Computing Facility . . . ”. One further similarsystem disclosed in U.S. Pat. No. 7,353,179 titled “System and methodfor handling the acquisition and analysis of medical data over anetwork” by Ott. Ott describes a system that receives and controlsHolter data from remote computers associated with the patients.

An example of Holter ECG system that uses a cellular architecture tomonitor and to transfer ECG signals via cellular network presented byFlach in U.S. Pat. No. 6,773,396 named “Cellular architecture and datatransfer methods for real time patient monitoring within medicalfacilities”. One more example of a similar system presented by Gerder inU.S. Pat. No. 7,301,452 titled “Care device with wireless datacommunication”. US 20090115628, 20090112769 and 20080224852 by Dicksdescribe a system configured to wirelessly receive data from a medicaldevice using the medical device transceiver and transmit the data to anintermediary device using the data relay transceiver.

US patent application 20060100530 by Kliot titled “Systems and methodsfor non-invasive detection and monitoring of cardiac and bloodparameters” discloses a “Method and system for long term monitoring ofone or more physiological parameters such as respiration, heart rate,body temperature, electrical heart activity, blood oxygenation, bloodflow velocity, blood pressure, intracranial pressure, the presence ofemboli in the blood stream and electrical brain activity are provided.”Kliot in his system actually provides a possibility of alert and“localization capabilities incorporating VHF, GPS, satellite and/ortriangulation location systems,” but his system is limited tophysiological parameters such as respiration, heart rate, bodytemperature, etc. and is not a holter system. Actually, Kliot mentionsholters in his prior art paragraphs as: “Although Holter and cardiacevent monitors are being used in attempts to diagnose and monitorvarious cardiac irregularities that are asymptomatic or infrequentlyexperienced, their limited data storage and analysis capabilities havereduced their application for wider ranging diagnostic and monitoringapplications. The success rate is rather low with these devices, sincethe Holter monitor seldom captures rare events in the typical,relatively short-term recording period and event monitor ispatient-triggered and user dependent. These systems could be improvedwith more substantial recording and data storage capability and betteranalytical systems. The Holter and cardiac event monitors also aretypically operated as stand-alone devices and are not interfaced withother devices collecting clinically useful patient data. Nonetheless,Holter and cardiac event monitoring are the only longer-term cardiacevent monitoring systems presently available.”

As a most sophisticated development of holters, there are a few thatprovide cardiovascular data analysis of several major cardiologicaldiseases and sent the data analyzed through wireless network. The mostadvanced of such a product is a Cardionet which presents the “MobileCardiac Outpatient Telemetry” product with real time analysis, automaticarrhythmia detection and wireless ECG transmission.

Clinical trial management is a second major aspect of the invention.

Effective clinical trial management systems relies on a means ofreal-time collection of data and performance measures to be able toreact instantly to the changes in performance of medicine or treatmentin the clinical trial participant, which is very important when relevantinformation belongs to the clinical trial where participant location maybe very diverse geographically. This is especially true in clinicaltrials of new medicines as clinical evaluations of new pharmaceuticalsin particular involve numerous evaluations at different stages ofdevelopment that often involve many sites spread throughout differentcountries and time zones.

Currently, clinical trial data mainly manually recorded on paper orentered manually via a keyboard to the computer. Alternatively,“paperless” data may be entered directly into a computer at a remotesite, in either manual or automated way. With advancements in computerscience there had been some advancement in clinical trials field. Thereare a number of prior art citations that disclose real-time clinicaltrial systems. One such example is provided by El Eman in US patentapplication 20070265881. El Eman discloses a system where real-timeinteractive patient form is introduced. Clinical trial participantsinsert data related to the clinical trial via the XML web-based form andthey can transfer it via the web to the centralized database of aclinical trial. Another similar system is disclosed in US patentapplication 20050055241 by Horstmann wherein a real-time clinical trialstudy documentation is provided and where a change to the documentationby an authorized user is made available in real time to one or moreother authorized users for tasks relating to the clinical trial studydocumentation. Another example of a similar system was disclosed in a USpatent application 20050038692 by Kane titled “System and method forfacilitating centralized candidate selection and monitoring subjectparticipation in clinical trial studies” wherein centralized remoteratings of subjects in clinical trial studies are introduced todetermine whether a candidate is a qualified subject for the clinicaltrial and/or in the actual assessment, or information collection, phaseof the clinical trial. US patent application 20040093240 by Shahprovides real-time clinical trial status monitoring at definableintervals and it is another variant of the prior art type above.

As a further development in the clinical trials industry, currentlythere are a few prior art citations where wireless data communicationhas been introduced. For one, US 20080228057 titled “Method and systemfor controlling data information between two portable apparatuses” byGraskov discloses a method and system of controlling data informationbetween two portable handheld apparatuses where information gatheredthroughout the clinical trial could be transferred wirelessly, and inparticular “lipid monitor, a pulse monitor, a lancet device, a storagecontainer, and a blood glucose monitor (BGM).” Unlike our disclosedinvention, no cardiological data is introduced here and no real-time andadaptive clinical trial features could be seen here. Another such systemis presented in US 20070156459 by McMahon that discloses a system forconducting a clinical trial of a pharmaceutical substance on a pluralityof trial participants that includes a central database and the remotecomputers being configured to receive predetermined trial data from oneor more trial participants. Yet another similar system is presented inUS 20080021341 titled Methods and Systems for Facilitating ClinicalTrials by Harris that involves a clinical trial for experimentaltherapies rather than for the pharmaceutical substance.

More sophisticated approach is presented in several prior art patentapplications wherein the data is collected wirelessly. One such priorart invention is US patent application 20080270181 titled “Method andsystem for collection, validation, and reporting of data and meta-datain conducting adaptive clinical trials” by Rosenberg. In 20080270181Rosenberg describes a system for centrally managing data in an adaptiveclinical trial or other adaptive process that is conducted at aplurality of geographically remote sites. Rosenberg discloses a systemthat collects data from remote sites in a clinical trial by the means ofinternet, telephone, wireless system, RSS feed or Atom feed. The systemalso provides interaction between central and remote sites to manage andresolve data discrepancies. The invention provides some improvement onthe abovementioned since it provides some ability to collect and processvarious forms of data in order to adjust actions related to the clinicaltrial but it still maintains the shortcomings of the prior art above.The data is not collected in real-time but rather collected through thepatient's visit to the remote clinical site and then the data could betransmitted by internet, wirelessly, etc. Still, unlike our invention,no real-time and personalized cardiological data analysis, response andadaptation are made.

An additional element of our invention is an alert-triggered permanentblood pressure measurement system.

Currently blood pressure measurement is done mainly when the patient isvisiting the physician or using a regular self-measurement home bloodpressure measurement device. Those measurements methods required animprovement since blood pressure results could vary during severalone-time measurements. Some 25% of the patients have higher bloodpressure when visiting the physician, for example. Accordingly,ambulatory blood pressure monitors systems have been created, one ofthose by a German manufacturer Ergoline named Ergoscan 24, another is byChinese manufacturer Contectmed “CMS06C ABPM Ambulatory Blood PressureMonitoring System”.

Additionally, there are a number of prior art inventions on the matterof ambulatory blood pressure systems and devices known in the prior art.For one, there is a U.S. Pat. No. 7,429,245 by Whitaker titled “Motionmanagement in a fast blood pressure measurement device”. That inventiondiscloses an apparatus and a method for measuring the blood pressure ofa vertebrate subject that uses an inflatable chamber with a sensor todetect signals indicative of a blood pressure of the subject during aninflation interval of the inflatable chamber. If secondary motion orartifact signals are detected, the apparatus and method determinewhether the secondary signals are below a predetermined value, and ifso, complete the measurement.

Another U.S. Pat. No. 5,447,161 discloses: “a process and measurementdevice for noninvasive determination of venous and arterial bloodpressure in the arteries of the human body, particularly in the fingerand toes. An occlusion band and peripherally thereto a sensor for thedetection of changes in the blood volume during the pressure-buildupprocedure is attached in these measurement areas”.

Another U.S. Pat. No. 6,632,181 titled “Rapid non-invasive bloodpressure measuring device” by Flaherty discloses a blood pressureambulatory measurement device that works by supplying an externalpressure to a portion of an artery and where the external pressure ispreferably between the systolic and diastolic pressure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 provides a general overview of the invented system and apparatus.

FIG. 2 shows the major hardware and software components of the inventedsystem and apparatus.

FIG. 3 graphically illustrates the personalized alerts thresholds forevery patient enrolled.

FIG. 4 is a schematic representation of the bi-directional communicationdata exchange between Holter/ECG of the patients and medical emergencyservices.

FIG. 5 provides a graphical illustration of the database and datamovement in the invented system.

FIG. 6 provides a graphical illustration of the wireless device'sdisplay panel.

FIG. 7 provides a graphical illustration of the clinical trialmanagement system.

DETAILED DESCRIPTION OF THE INVENTION

In the following discussion, numerous specific details are set forth toprovide a thorough understanding of the present invention.

The invention deals with two major aspects: as a first aspect, itprovides a real-time automated cardiovascular personalized monitoringsystem for permanently monitoring the abnormalities in patient'scardiovascular data through the use of permanent Holter/ECG device andgenerating alert signals representative of certain abnormalities of thepatient according to individual alert parameters adjusted for everypatient enrolled; as a second aspect it provides a system for quickreal-time (or very near real-time) response in clinical trials to theadverse effects related to use of medications, as well as to theabnormalities alerts in general, as detected by the personalizedcardiovascular monitoring system of the first aspect.

The above-mentioned prior art examples lack the feature ofevent-triggered blood pressure measurements which could be particularlyimportant to chronic heart patients as well as other patients with heartdisease developments. This feature will help physicians and clinicaltrial investigators know the blood pressure measurements at the exacttime when an abnormality cardiac alert is detected by the Holter/ECGsoftware.

Other features and advantages of the present invention will be apparentfrom the following description taken in conjunction with theaccompanying drawings, in which like reference characters designate thesame or similar parts throughout the figures thereof.

A Holter Electrocardiogram—often referred to as Holter EKG or ECG—is atest that measures the electrical activity of the heart for a prolongedperiod of time, typically 24 or 48 hours, on an outpatient basis. Holterdiffers from a resting ECG in that a resting ECG records a very smallportion of your heart's activity, less than one quarter of one percentof your daily heartbeats. The resting ECG is taken while you are at restand, therefore, does not show how your heart will react to normal dailylife.

Every patient enrolled into the disclosed system receives the Holter/ECGdevice for the permanent use and it works continuously even when thepatient does not feel any pain or other uncomfortable symptoms.

The system includes a number of Holter/ECG electrodes/sensors, which areaffixed to the patient and they generate signals indicative of certaincardiovascular activities being carried out by the patient (101). Thesesignals could be obtained by the means of either digital or analogueHolter/ECG. In case where they are obtained by the means of analogueHolter/ECG, they will be then digitized. In such a case ananalogue-digital converter will be used to convert the analogue signalto the digital signal.

Cardiac activity of the patient obtained from the electrodes will berecorder by the Holter/ECG recorder (102).

The patient's cardiovascular activities recorded by 102 will then beanalyzed by Holter/ECG personalized analysis software (103). Thisspecial personalized Holter/ECG software will be used in decoding of thecardiovascular data of the patient and, following that will detectabnormalities in the Holter/ECG signals automatically, in real-time andin accordance to the personal cardiological and general medical data ofthe patient (104). Such personalized adjustments are especiallyimportant for the chronic patients.

Those abnormalities will be classified according to their severityclassification—some abnormalities will only be stored in a file of theparticular patient, others will require him to take a medicine, otherswill require a visit to the doctor, while others will require calling anambulance without any delay. A special medical classification ofHolter/ECG-detected abnormalities will be applied. Such medicalclassification will be produced by the medical experts and in accordancewith the usual cardiovascular medical classifications, such as theMinnesota Code.

Such Holter/ECG software will be integrated inside the wireless device(as a part of it) capable of bi-directional transmittance of informationin a wireless phone network. The software will be built-in as a chip onthe board of such a wireless device. A regular existing cellphonehandset provides an example of such wireless device (105).

Such wireless device will send abnormalities alerts detected wirelessly,using cellular network, to a medical dispatcher center (106).

A real-time medical response such as sending an ambulance will begenerated by the medical emergency center according to thoseautomatically detected signals in accordance with abnormalitiesclassification (107). Actually, each abnormality alert will beclassified according to the severity of the disease alerted. When theabnormality detected justifies an urgent alert, the Holter/ECG will usethe cellular network to transfer the emergency signal to the medicalcenter. There the signals will be attended by the medical dispatcher.This will allow the dispatcher working in the center to send ambulanceto the patient according to his location detected by the means of GPSor/and cellular network location.

FIG. 2 graphically summarizes major hardware and software components inthe invented system and apparatus (201).

202 illustrates recording of physiological signals corresponding tocardiac activity collected by external electrodes applied to a patient,comprising a set of electrodes. Preferably, a 12-lead electrode systemwill be used for more accurate cardiac signals collection.

203 show a Holter/ECG converter and amplifier hardware components. Ananalogue-digital converter will be used only in case of analogueHolter/ECG to convert the analogue signal to the digital signal.

204 show a Holter/ECG recorder. A regular Holter/ECG recorder could beused in the invented system. It will be well understood by those skilledin the art that each regular Holter/ECG recorder will provide merely anexemplary component, and that the present invention is by no meanslimited to any particular Holter/ECG recorder. The holter is equippedwith the first-in first-out feature, wherein the data recorded firstwill be deleted first and the data recorded last will be deleted last.

205 show a Holter/ECG personalized analysis software used to analyze thepatient's cardiovascular activities to detect abnormalities. Thesoftware is capable of analyzing and detecting widely known cardiacabnormalities. The software is also capable of multiple ECG scanningmodes for reviewing data and capturing cardiac abnormalities. On anystage the software is able to produce as an output a final report withsummary of all cardio action recorded and with details regarding allcardiological abnormalities detected. The software provided to eachpatient will be personalized according to personal health, age and sexcharacteristics. For such personalization, each patient enrolled intothe system will have to complete the personal questionnaire where hewill indicate his usual blood pressure, pulse, and other vital signs. Tothis initial enrollment questionnaire, the doctor will add recent ECGdata of this patient.

Based on this initial enrollment data, for each patient and for eachcardiological disease there will be defined a predetermined set ofthreshold parameters, different every indicator indicative of a certaindisease, each of said threshold alert parameters being individuallyadjustable by the physician during the operation of the holter. This isof importance since there are many chronic patients that for them thebasic default threshold alert parameters will produce many alerts thatare not of any clinical significance. Therefore, ECG recording of suchchronic patient will differ significantly from the ECG recording of acompletely healthy person. For a simple example, for the person withusual heart beats rate of 100 per minute, sinus tachycardia alertthreshold should be placed not at 100 but, lets say at 120 heart beatsper minute.

Additionally to the personally adjusted alert threshold parameters,alert parameters will be adjusted when the person has taken a medicine,a meal, has been engaged in sporting activity or has been asleep. Thisinformation will be recorded when the patient will push the Medicine,Meal, Sports and Sleep buttons—Medicine that will be pressed when thepatient has taken any particular medicine, Sports that will be pressedwhen the patient will be engaged in a sporting activity; Meal that willbe pressed when the patient will have a meal; Sleep that will be pressedwhen the patient will start/finish his sleep; additionally an Emergencybutton will be provided for quick contact of the emergency center.Initial personalized abnormality “resting” alert thresholds will be thenupdated based on the inputted patient data above.

Personalized abnormalities alerts thresholds will also be updated inreal-time during the ongoing permanent Holter/ECG monitoring by takinginto consideration a new cardiological data obtained on the patient,analyzing such data, including a relevant personal abnormalities alertsthresholds, and producing a new personal alerts thresholds based on thisdata. This will be done by initially obtaining as an input from thecentralized database initial patient personalized emergency alertsthresholds, then obtaining as an input a real-time cardiological data ofthe patient from the Holter/ECG monitoring, including patientpersonalized emergency alerts thresholds previously taken and, then, byupdating said patient personalized emergency alerts thresholds with thenewly obtained data during the real-time Holter/ECG cardiac monitoring(FIG. 3 graphically illustrates the personalized alerts thresholds forevery patient enrolled).

By looking at the abovementioned example, sinus tachycardia alertthreshold will be different for the same person at resting status andperson at “Sports” status as heart beats rate is different for the sameperson at resting status and at “sports” status.

The collected ECGs contain certain types of noise, which are typical forHolter ECG recordings. Such noise is the baseline noise (e.g.respiration), high frequency noise, line frequency noise, beat-likeartifacts (because of temporary pressure on electrodes) and high rangenoise (in case electrodes become loose). The modern holter/ECG analysissoftware can analyze, recognize and cutout the noise elements to providemore accurate analysis and detection. Noise removal is an important partof getting a correct cardiovascular diagnosis.

Element 206 shows the wireless device equipped with the modem andcellphone antenna capable of transmitting data.

Element 207 shows the LCD-type or touch screen display panel that thewireless device 206 equipped with.

Element 208 shows the custom-made client's input buttons of thisconfiguration of the wireless device 206 as the system is provided withinput capability for enabling the patient to input data such as the timeof meal intake, time of sleep, etc.

Element 209 illustrates that the wireless device 206 can be configuredwith the GPS location data transmitter/receiver as well as a usercommunication device. It should be noted that in this configuration GPScapabilities are an advantage but not absolutely necessary fornavigational directions.

Element 210 illustrates that a special blood pressure system will beincorporated inside the invented system and device. High blood pressureis a common risk factor for heart attacks, strokes and aneurysms, sopermanent monitoring is critically important. Additionally, in clinicaltrials it is important to use this feature, especially when it isnecessary to see how well your medicine is working to control your highblood pressure. The blood pressure system will consist of blood pressuresensor, blood pressure recorder and inflatable cuff chamber. The systemwill work on a permanent basis and it will measure the blood pressure atevent-triggered basis, i.e. it will measure blood pressure when theholter/ECG will detect an abnormality event (blood pressure measurementsat predetermined time intervals, say once an hour will also be made).This will help to diagnose a correct cardiological disease and toindicate long-time blood pressure measurements. For the purpose ofpermanent blood pressure monitoring, a non-invasive blood sensor will beused. A solid, small-sized blood pressure sensor, preferably cuff-less,worn over a palpable artery could be utilized to measure arterial bloodpressure.

As abovementioned, the system will further include the wirelessarchitecture and infrastructure as an integral part of the disclosedHolter/ECG system for bi-directional communication between the patientsand the medical emergency center (401). Such a device will transmitabnormalities alerts from the Holter/ECG to the medical dispatcher. TheHolter/ECG device will then work in cellular network. The system willwork in different wireless protocol systems including Integrated DigitalEnhanced Network (IDEN), GSM, CDMA, etc.

IDEN is a preferable wireless system in the implementation of thisinvention since it is the best system for open way two-wayscommunication.

Using the wireless phone network will also allow to receive an exactlocation of the patient's whereabouts in case that there is a need tocall an ambulance to that particular location. Most modern wirelessphone networks can determine the location of the cellular handset withthe accuracy of about 100 meters.

Patient's exact location could also be detected through the use of theGPS technology. For that, a special GPS receiver/transmitter will befurther integrated within the device (402).

In case that an abnormality has been detected and an abnormality alertwill be created, the medical emergency center (403) will send, in caseof need, an emergency medical support, such as an ambulance to thepatient (404). The medical ambulance will be called to the patient'smost recent location obtained by the means of wireless network locationand/or GPS-based location. The system will check the patient's currentlocation and location of each ambulance and the nearest ambulance willbe sent.

The system will further include a centralized medical database (501)where personal medical records for each patient will be stored, and towhere all cardiological alerts and other cardiological data will arrive.Thus, FIG. 5 provides for databases and data movement in the system.

Such centralized database will be available for viewing, monitoring andanalysis both on-location and through the Internet. For the Internetuse, a special web-based portal will be developed.

An extensive statistical work will be applies to analyze such data foreach patient separately and for all patients together as certainstatistical averages and other statistics will be created. The latterwill be helpful in producing clinical trials and for feeding clinicaltrial companies and pharmaceutical companies, in particular, with themedical data of each patient. For that a special clinical trial databaseinterconnected with the centralized database will be created (502).

Full information database of all patients will be also produced as wellas statistical parameters in regard to certain levels of cardiologicalactivity and, particular cardiological parameters to suit a certainclinical trial need. For example, some pharmaceutical firm may requirean adverse events database records for patients taking some sort ofmedicines that they develop or already developed.

For each patient enrolled, a medical file on record in a medicaldispatcher center will be created (503). This medical file of thepatient will include a full medical history of the patient, including ahistory of cardiovascular abnormalities, history of surgery operationsand procedures, normal levels of psychological and cardiovascularparameters, such as pulse, blood pressure, etc. In particular, thepatient medical record will include personal thresholds to determine ifthe event is irregular for the particular patient.

Information on medicine taken, on meals taken, on sleep and sportsactivities will be provided to the patient's personal file (504) and tothe centralized database through wireless communication.

Abnormalities alerts data (505) as well as medical response to the alertdata (506), alert treatment data (507) and results of alert treatment(medical condition after the treatment) (508) will also be provided tothe patient's personal file and to the centralized database throughwireless communication.

Besides regular updates on patients and abnormalities events, newmedical scientific data update will be inputted to the centralizeddatabase (509) to keep it updated with the latest medical sciencedevelopments (discoveries of new diseases, new methods of treatment,etc.). The new medical scientific data update will be also provided tothe analysis software and will be consequently updated at patient'sHolter/ECG device (510).

FIG. 6 provides a graphical illustration of the wireless device andespecially of it display panel. In the preferred embodiment the displayunit could be a color LCD or a touch screen color display device easilyaccessible to the patient (601).

The cardiological abnormalities alert signals could also be shown on thescreen of such patient's wireless device (602). This would be doneaccording to patient's express will to receive the alerts or not. Somepatient's may choose to not accept to receive such alerts on theirdevice from psychological reasons.

To help obtaining more accurate cardiological information, the wirelessdevice of the patient will also be equipped with four custom-producedbuttons:

Medicines (603)

Meal (604)

Sleep (605)

Sport (606)

Clicking on the Medicines button will open several submenus where ineach submenu there will be a name of each medicine that the patienttakes. For that, the patient will submit information on the medicines heintakes when he initially enrolls into the system. After the patienttakes that particular medicine, he will press on the medicine takenbutton for that particular medicine. Immediately, this information willbe transferred using the wireless phone system to the central patientsdatabase and will be stored there in the file of that particularpatient.

In addition “real-time adaptive approach” of the invention allows forinstant modification of parameters of the clinical trial as it involvesand as new clinical trial data is arrived. For example, the inventionallows the study investigator to modify amount of medicine the certainparticipant takes, to order the participant to stop taking the medicine,to pull the participant of the trial, to pause or to stop a trial.

The invention further provides the capability of electronically managingsubmitted data to ensure that discrepancies are identified, as well asan interactive component for communicating with clinical sites toresolve data discrepancies, and a flexible, computer network-based(e.g., internet or intranet) system of reporting on data and performanceindicators to sites, organizations managing the trial, and individualsinvolved with oversight.

It will be understood by those skilled in the art that these are merelyexemplary components, and that the present invention is by no meanslimited to any particular implementation or combination of such systems.

Additionally, the patient may hit the Meal button after hestarts/finishes his meal and may use the Sleep button when going tosleep and when waking up. This data will also be transferred using thewireless phone system to the central patients database and will bestored there in the file of that particular patient.

The patient may click on the Sport button whenever he starts or finisheshis sporting or exercise activities. Such data will also simultaneouslyarrive to the central database and to the personal medical file situatedthere. That will help determine patient's diagnosis more accurately, andwill also provide information for clinical trial use.

Such Medicines, Meal, Sleep, Sport data will assist in making thecorrect diagnosis and will also provide valuable information for thedatabase in regard to clinical trial management companies, andespecially for the pharmaceutical companies.

A special Emergency Center button (607) will be additionally installedat such a wireless device to enable the patient to call a medicalemergency center with a press of one button without any delays.

The wireless device will have a multilingual capability to give an easyconvenient access to most patients. A special rechargeable long-lifebattery should be used to provide a long lasting use of the wirelessdevice.

So, more particularly, the present invention also relates to networkarchitecture, and an associated communications protocol, forfacilitating the efficient and reliable exchange of information betweenportable wireless devices and centralized monitoring stations.

The second major aspect of the invention describes a real-time automatedsystem and apparatus for conducting clinical trials in the medical fieldby providing a fully integrated ability to handle real-time datacollection from remotely situated participants of the clinical trial andby providing a real-time analysis and response to the data collectedfrom the participants (graphically illustrated in FIG. 6). The inventionparticularly relates to a clinical trial of pharmaceutical substance(medicine, drug) providing clinical trial team with the ability toquickly react to the clinical trial data. This is especially useful forPhases I, II, III of the clinical trial. The invention looks to beparticularly useful for Phase III of the clinical trial since Phase IIIstudies generally involve randomized controlled large patient groups(300-3,000 or more depending upon the disease/medical conditionstudied). Phase III studies normally conducted on the “multicenter”basis, meaning that patients are situated at different locations, andsometimes even in different countries. Because of their size andcomparatively long duration, Phase III trials are the most expensive,time-consuming and difficult trials to design and run, especially intherapies for chronic medical conditions. The invented system andapparatus could also be used for Phase IV trial (also known as PostMarketing Surveillance Trial) that involves the safety surveillance(pharmacovigilance) and ongoing technical support of a drug after itreceives permission to be sold.

Since the invented system is designed to respond to changingcircumstances is a central part of being able to successfully handle aclinical trial, the invention provides a “real-time adaptive approach”to conducting clinical trials. An adaptive approach to clinical trialmeans a system for providing automatic real-time medical response inclinical trials in medical field to detection of risks of adverseeffects resulting from use of at least one medication, based onautomatic cardiac abnormality alert detection from the Holter/ECG data.

In most clinical trials there are more than one medication or medicalprocedure being tested, in others just there is just one medication ormedical procedure being trialed. So, in every clinical trial it isnecessary to collect previously taken medical input data regardingthat/those medication or medical procedure.

Then, for each medication/s or medical procedure a safe profile isdetermined, and safe profile parameters are defined then. Such safeprofile parameters will be determined individually for every trialparticipant enrolled into the clinical trial based on his initialenrollment data.

A total number of enrolled trial participants will be determined beforethe start of the clinical trial. Then, the participants will berandomized and two or more randomized groups of participants will becreated. Following the randomization, the system will determine whichtrial participants receive the pharmaceutical substance/procedure aspart of the clinical trial and which trial participants receive aplacebo (701).

Then the participants from both groups will receive permanent wirelessHolter/ECG devices (702). The participants will also receive alogin/password credentials to be able to access the clinical trialwebsite and to have the ability to receive orders from clinical trialinvestigators through the Internet. Such devices are described above inmore details.

The abovementioned device will detect personalized abnormalities incardiac parameters of clinical trial participants based on individualprofile parameters of each participant. Additionally, specialpersonalized safe profile parameters in regard to clinical trialtreatment will be concluded for each participant. Such individual safeprofile parameters will take into consideration general safe parametersfor the treatment in conjunction with personal health parameters of theparticipant (703).

For the abnormality alert detected that is outside of the personal safeprofile parameters for the particular participant, the abnormality alertwill be assessed in combination with other drugs, foods, vitamins,sporting activities and other parameters data and it will be determinedif an alert constitutes adverse effect risk requiring emergency medicalresponse (704).

Based on personalized abnormality alert detection, clinical trialinvestigators team will choose from a variety of possible medicalresponses based on the severity and frequency of adverse effect cases(705). For one, clinical trial investigators may decide to order theparticipant to change the dosage of the medication/medical treatment(706). Another option is to transmit the clinical trial participant anorder to stop taking the said medication/medical treatment and/or starttaking another medication/medical treatment instead (707). If there areserious adverse effect risks that may risk clinical trial participant'shealth or even life, the investigators may transfer the order to pullthe participant out of the clinical trial (708). All those orders may betransmitted wirelessly using the two-way communication capabilities ofthe wireless device. For another option, those orders may be transmittedby phone or through the Internet.

If clinical trial investigators team decide that the number/severity ofadverse effects risks is critical, they may decide to stop the clinicaltrial and, consequently, send an appropriate wireless/phone/web order toall clinical trial participants (709).

The invented system further includes the feature of providing a numberof online/offline reports, including medical, financial and others,relating to the clinical trial conducted.

What is claimed:
 1. A method for providing cardiovascular personalizedpatient alerts for a plurality of patients, comprising the steps of: a)maintaining physiological data and cardiac data for each of saidplurality of patients, respectively, said cardiac data selected from thelist consisting of ECG, EKG, blood pressure, heart rate; b) creatingpersonalized resting alert thresholds for each of the patients,respectively, based on the physiological data and the cardiac data wheneach of said patients are respectively at rest; c) providing eachpatient with a respective wireless Holter/ECG-type device which is wornon each patient, each Holter/ECG-type device having respective buttonsincluding a Medicine button for pressing when the patient has taken anyparticular medicine, a Sports button for pressing when the patient willbe engaged in a sporting activity; a Meal button for pressing when thepatient will have a meal and; a Sleep button for pressing when thepatient will start/finish his sleep; d) providing each of said patientswith respective abnormality alert thresholds, wherein each of saidthresholds is respectively different between each of said patients basedon each patients' respective physiological data or cardiac data whereinthe alert thresholds being exceeded is detected based on saidphysiological data or cardiac data which is obtained; e) updating saidalert thresholds provided in step d) for each of said patients, based onsaid respective resting alert thresholds, respective cardiac dataprovided by each Holter/ECG-type device as a result of monitoring eachof said patients, respective abnormality alert thresholds and actuationof said respective buttons; f) generating, without human involvement, arespective diagnosis for each of said patients based on data provided byeach of said Holters/ECGs, said updated alert thresholds, and whetherany of said buttons have been pushed, wherein said respective diagnosisis generated by a respective one of said Holters/ECGs prior to step g);and; g) transmitting said respective diagnosis from said wirelessHolter/ECG-type device, for a medical response to be provided at alocation where one of said patients is located if said generateddiagnosis is predetermined to be responded to by the medical response,wherein said medical response includes requesting providing of anambulance to said location where said one of said patients is located.2. The method of claim 1, further comprising the step of: h) storingsaid physiological data and said cardiac data for each of said patients,respectively, at a centralized database.
 3. The method of claim 2,wherein step h) further comprises: signaling via a cellular network tothe centralized database at a medical emergency center.
 4. The method ofclaim 2, wherein the wireless device further includes means foranalyzing statistical data received from the centralized database. 5.The method of claim 4, wherein the wireless device includes means forsending the analyzed statistical data to clinical trial providers in aformat acceptable to the clinical trial providers.
 6. The method ofclaim 1, wherein each respective wireless Holter/ECG-type deviceincludes a cellular mobile telephone, a multimedia phone or a personaldigital assistant (PDA).
 7. The method of claim 1, further comprisingthe step of: i) determining an exact location of each wirelessHolter/ECG-type device by obtaining a wireless phone location of thewireless device or a GPS equipment-based location of the wirelessdevice.
 8. The method of claim 1, wherein step g) further comprisessending an ambulance in response to the transmitting.
 9. The method ofclaim 8, wherein an exact location of each wireless device is obtainedby obtaining a wireless phone location of each wireless device or a GPSequipment-based location of each wireless device, and the ambulance issent to each patients' exact location.
 10. The method of claim 1,wherein the wireless device further includes a blood pressure apparatus,and further comprising the step of: transferring said cardiac dataincluding blood pressure after the signaling of step f).
 11. The methodof claim 1, further comprising blood pressure measuring means, suchmeans comprising: an inflatable cuff chamber operable to be inflatedduring an inflation interval and deflated during a deflation interval; asensor coupled to said inflatable cuff chamber and configured to measurea blood pressure; and a control electronic module configured forcontrolling the operation of said inflatable cuff chamber and saidsensor.
 12. The method of claim 11, further comprising the step of:taking a permanent continuous blood pressure measurement inpredetermined time-intervals.
 13. The method of claim 12, furthercomprising the step of: transmitting wirelessly a personalizedabnormality blood pressure alert to the medical emergency center basedon personalized blood pressure measurements thresholds, the saidthresholds being determined individually for each patient, whereinthreshold limits are limit of normal blood pressure for the patient. 14.The method of claim 13, further comprising the steps of: obtaining as aninput from the centralized database initial patient personalized bloodpressure emergency alerts thresholds; obtaining as an input real-timecardiological data of the patient from the continuous blood pressuremeasurement, including the initial patient personalized blood pressureemergency alerts thresholds; updating said initial patient personalizedblood pressure emergency alerts thresholds with the real-timecardiological data.
 15. The method of claim 1, wherein step d) includesthe step of creating the updated alert thresholds based on said cardiacdata which is provided after said respective buttons have been actuated.16. A method according to claim 1, wherein said medical responseincludes sending a closest ambulance to said patients' location based onsaid GPS equipment-based location.
 17. A method for monitoringcardiovascular activity of patients, comprising the steps of: creatingpersonalized resting alert thresholds for each of said patients,respectively, based on physiological data and cardiac data when each ofsaid patients are respectively at rest; obtaining data relating to thecardiovascular activity of the patients; generating abnormality alertthresholds for said patients based on said data and said resting alertthresholds, and providing each of said patients with respectiveabnormality alert thresholds, wherein each of said thresholds isrespectively different between each of said patients based on eachpatients' respective physiological data or cardiac data wherein thealert thresholds being exceeded is detected based on said physiologicaldata or cardiac data which is obtained; detecting, without humaninvolvement, abnormalities in the cardiovascular activity of the patientby comparing the obtained data with personalized cardiovascular activitythresholds for the patient; generating alerts based on the detectedabnormalities; modifying the thresholds based on the thresholds beingpreviously exceeded; generating a diagnosis prior to transmitting thealerts to the medical emergency center; transmitting the alerts to amedical emergency center over a wireless network; and receiving aresponse from the medical emergency center over the wireless network.18. A method according to claim 17, wherein a closest ambulance is sentto said patient based on GPS data transmitted when said alerts aretransmitted.
 19. A method for providing real-time medical response toabnormal cardiovascular activity of patients, comprising the steps of:creating personalized resting alert thresholds for each of the patients,respectively, based on physiological data and cardiac data when each ofsaid patients are respectively at rest; providing to the patientsrecorder devices for continuously monitoring the cardiovascular activityof the patient, said recorder device for generating abnormality alertthresholds; providing each of said patients with respective abnormalityalert thresholds, wherein each of said thresholds is respectivelydifferent between each of said patients based on each patients' restingalert thresholds and each patients' respective physiological data orcardiac data wherein the alert thresholds being exceeded is detectedbased on said physiological data or cardiac data which is obtained;receiving, without human involvement, at a medical emergency center a)alerts indicating the abnormal cardiovascular activity of the patientsfrom the recorder devices via a wireless network, and b) diagnosis; andissuing the medical response to the patient in real-time based on thereceived alerts.
 20. A method according to claim 19, wherein a closestambulance is sent to said patient based on GPS data transmitted whensaid alerts are transmitted.